Post-Progression Survival in Patients with Non-Small Cell Lung Cancer with Clinically Acquired Resistance to Gefitinib

Most patients with tyrosine kinase inhibitor (TKI)-sensitive non-small cell lung cancer (NSCLC) eventually develop acquired resistance to TKIs. Factors that affect TKI-sensitive patient survival after progression during TKI treatment remain unknown. We attempted to identify factors that affected post-progression survival. We retrospectively reviewed 81 advanced NSCLC patients with disease progression following tumor response and durable (≥ 6 months) disease stabilization with first-line or second-line gefitinib. Post-progression survival (PPS) and characteristics were investigated and compared in patients who did (n = 16) and did not (n = 65) resume TKIs. Most patients were female never-smokers with adenocarcinoma. Median overall PPS was 10.3 months (95% confidence interval [CI], 7.458-13.142). Age, gender, smoking history, histology, Eastern Cooperative Oncology Group performance status at gefitinib initiation, initial stage, and platinum-based chemotherapy after gefitinib were not significant predictors of PPS. Pemetrexed use after gefitinib significantly improved PPS (18.5 vs 8.6 months; hazard ratio [HR], 0.45; P = 0.008). Gefitinib reuse tended to lengthen PPS but was insignificant in multivariate analysis (27.4 vs 8.8 months; HR, 0.53; P = 0.095). NSCLC patients assumed to have clinically acquired resistance to TKIs had relatively long PPS. TKIs reuse or pemetrexed use after progression with gefitinib may improve PPS.     

Predicting Recurrence Using the Clinical Factors of Patients with Non-small Cell Lung Cancer After Curative Resection

We present a recurrence prediction model using multiple clinical parameters in patients surgically treated for non-small cell lung cancer. Among 1,578 lung cancer patients who underwent complete resection, we compared the early-recurrence group with the 3-yr non-recurrence group for evaluating those factors that influence early recurrence within one year after surgery. Adenocarcinoma and squamous cell carcinoma were analyzed independently. We used multiple logistic regression analysis to identify the independent clinical predictors of recurrence and Cox''s proportional hazard regression method to develop a clinical prediction model. We randomly divided our patients into the training and test subsets. The pathologic stages, tumor cell type, differentiation of tumor, neoadjuvant therapy and age were significant factors on the multivariable analysis. We constructed the model for the training set with adenocarcinoma (n=236) and squamous cell carcinoma (n=305), and we applied it to the test set with adenocarcinoma (n=110) and squamous cell carcinoma (n=154). It was predictive for the in adenocarcinoma (P<0.001) and the squamous cell carcinoma (P=0.037), respectively. Our results showed that our recurrence prediction model based on the clinical parameters could significantly predict the individual patients who were at high risk or low risk for recurrence.     

Clinical Significance of Aberrant Wnt7a Promoter Methylation in Human Non-Small Cell Lung Cancer in Koreans

The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

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RET polymorphisms might be the risk factors for thyroid cancer

Aims: The purpose of the study is to investigate the relationship between rs1799939, rs1800858 and rs74799832 polymorphisms of RET with thyroid cancer (TC) susceptibility. Methods: Genotypes distribution of control groups were tested by Hardy-Weinberg equilibrium (HWE). Rs1799939, rs1800858 and rs74799832 polymorphisms of RET were researched in 135 patients with TC and 135 healthy people using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the association between RET polymorphisms and the risk of TC by Chi-squared test. Results: Genotypes frequencies of the control group were consistent with HWE. The frequency of genotype AA and allele A in rs1799939 were significantly higher in patients with TC than controls (OR=3.768, P=0.046; OR=1.695, P=0.035). Genotype GG and allele G of rs1800858 remarkably increased the risk of TC (OR=2.149, P=0.039; OR=1.45, P=0.039). Moreover, CC genotype and C allele in rs74799832 polymorphism was related with TC susceptibility. (OR=2.28, P=0.049; OR=1.566, P=0.049). Conclusion: In present result, RET rs1799939, rs1800858 and rs74799832 polymorphisms might be the risk factors for TC.     

Prognostic Significance of Initial Platelet Counts and Fibrinogen Level in Advanced Non-Small Cell Lung Cancer

Thrombocytosis and coagulation systems activation are commonly associated with disease progression and are suggested poor prognostic factors in patients with malignancies. This study aimed to investigate the prevalence and prognostic significance of thrombocytosis and elevated fibrinogen levels in patients with advanced non-small cell lung cancer (NSCLC). Initial platelet counts and fibrinogen levels were reviewed in 854 patients with histologically proven NSCLC. Thrombocytosis was defined as platelet counts > 450 × 10⁹/L. A serum fibrinogen level > 4.5 g/L was considered high. At the time of diagnosis, initial platelet counts and serum fibrinogen levels were evaluated before treatment. Clinicopathologic data including histological type, tumor, node, metastasis (TNM) stage, performance status, treatment method, and survival time were evaluated. Initial thrombocytosis was found in 6.9% of patients, and elevated fibrinogen levels were found in 55.1% of patients. Patients with thrombocytosis had a significantly poorer prognosis than patients with normal platelet counts (P < 0.001). In multivariate survival analysis, thrombocytosis was an independent prognostic factor (P < 0.001). An elevated serum fibrinogen level was associated with poor prognosis (P < 0.001). In conclusion, initial thrombocytosis and a high fibrinogen level are independent factors for predicting poor prognosis in patients with advanced NSCLC.

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Influence of Methylenetetrahydrofolate Reductase C677T Polymorphism on the Risk of Lung Cancer and the Clinical Response to Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer: An Updated Meta-Analysis

Purpose

Methylenetetrahydrofolate reductase (MTHFR) has been implicated in lung cancer risk and response to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). However, the results are controversial. We performed meta-analysis to investigate the effect of MTHFR C677T polymorphism on lung cancer risk and response to platinum-based chemotherapy in advanced NSCLC.

Materials and Methods

The databases of PubMed, Ovid, Wanfang and Chinese Biomedicine were searched for eligible studies. Nineteen studies on MTHFR C677T polymorphism and lung cancer risk and three articles on C677T polymorphism and response to platinum-based chemotherapy in advanced NSCLC, were identified.

Results

The results indicated that the allelic contrast, homozygous contrast and recessive model of the MTHFR C677T polymorphism were associated significantly with increased lung cancer risk. In the subgroup analysis, the C677T polymorphism was significantly correlated with an increased risk of NSCLC, with the exception of the recessive model. The dominant model and the variant T allele showed a significant association with lung cancer susceptibility of ever smokers. Male TT homozygote carriers had a higher susceptibility, but the allelic contrast and homozygote model had a protective effect in females. No relationship was observed for SCLC in any comparison model. In addition, MTHFR 677TT homozygote carriers had a better response to platinum-based chemotherapy in advanced NSCLC in the recessive model.

Conclusion

The MTHFR C677T polymorphism might be a genetic marker for lung cancer risk or response to platinum-based chemotherapy in advanced NSCLC. However, our results require further verification.     

Genotyping analysis of 3 RET polymorphisms demonstrates low somatic mutation rate in Chinese Hirschsprung disease patients

Background: Genetic mosaicism has been reported for both coding and non-coding sequences in the RET gene in Hirschsprung disease (HSCR) patients. This study aimed to investigate somatic mutation rate in Chinese population by comparing both homozygous genotype percentage and risk allele frequency of 3 RET single nucleotide polymorphisms (SNPs) among blood and colon samples. Methods: DNA was extracted from 59 HSCR blood samples, 59 control blood samples and 76 fresh frozen colon tissue samples (grouped into ganglionic, transitional and aganglionic level). Genotype status of rs2435357 and rs2506030 was examined by competitive allele specific hydrolysis probes (Taqman) PCR technology, and rs2506004 was examined by Sanger sequencing. Homozygous genotype percentage and risk allele frequency were calculated for each type of sample and compared by chi-square test. P<0.05 was regarded as being statistically significant. Results: Colon tissue DNA samples showed similar frequency of SNPs as that of the blood DNA samples in HSCR patients, both of which are significantly higher than the control blood group (rs2435357 TT genotype: 71.2%, 74.7% versus 22.0% in HSCR blood, HSCR colon and control blood DNA respectively, P=0.000; rs2506004 AA genotype: 72.4%, 83.1% versus 25.5%, P=0.000; rs2506030 GG genotype: 79.7%, 77.2% versus 54.2%, P=0.000 and 0.004). With respect to DNA extracted from ganglionic, transitional and aganglionic levels, no statistically significant difference was demonstrated in those 3 regions (rs2435357: P=0.897; rs2506004: P=0.740; rs2506030: P=0.901). Conclusion: Our data does not support the notion that high frequency of somatic changes as an underlying etiology of Chinese HSCR population.     

Interactive Effect of Smoking and NQO1 Haplotypes on Lung Cancer Risk

The role of genetic polymorphisms of NAD(P)H:quinone oxidoreductase 1 (NQO1), which is known to be related to carcinogen metabolism and oxidative status, was evaluated for lung cancer development. The genotypes of two NQO1 polymorphisms, namely, IVS1-27C>G and Ex6+40C>T, were determined in 616 lung cancer cases and 616 lung cancer-free controls and haplotypes composed of the two polymorphisms were estimated. In the evaluation of the effect of the NQO1 genotypes or diplotypes, we did not find any significant association with lung cancer risk after adjusting for body mass index and smoking status. However, when we evaluated the effect of the NQO1 diplotypes for lung cancer risk in combination with smoking, smokers without the C-T/C-T diplotype showed a significantly increased risk of lung cancer compared with nonsmokers without the C-T/C-T diplotype (adjusted OR, 2.2; 95% CI, 1.67-3.02), and smokers with the C-T/C-T diplotype showed the highest OR of lung cancer (adjusted OR, 2.7; 95% CI, 1.78-4.21). Moreover, a trend test showed an additive interaction between smoking and the NQO1 C-T/C-T diplotype (P_trend < 0.01). The additive effect of smoking and the NQO1 C-T/C-T diplotype was more apparent in squamous cell carcinoma, although this effect was statistically significant in all lung cancer cell types (all cell types, P_trend < 0.05). This result suggests that haplotypes of the NQO1 gene play an important role in the development of lung cancer by interaction with smoking.

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The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma

Purpose

This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients.

Materials and Methods

Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing.

Results

The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G→A or C→T) rather than a transversion mutation (G→T or G→C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation.

Conclusion

Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.     

Calcified Pulmonary Nodules Identified in a 350-Year-Old-Joseon Mummy: the First Report on Ancient Pulmonary Tuberculosis from Archaeologically Obtained Pre-modern Korean Samples

We found calcified pulmonary nodules in a middle-aged female mummy discovered from 350-yr-old Joseon tomb of Korea. In the CT scan, we found six radiopaque nodules in right lung, through the levels of thoracic vertebrae 1 to 6. We also found presumptive pleural adhesions in right thoracic cavity of CT images. We re-confirmed radiological findings by our post-factum dissection on the same mummy. By the differential diagnosis, we speculate that the radiopaque calcification nodules and associated pleural adhesion could have been caused by tuberculosis. This is the first-ever report on the pulmonary tuberculosis identified in archaeologically obtained, pre-modern Korean samples.     

Genetic Variants in the Wnt Signaling Pathway Are Not Associated with Survival Outcome of Non-Small Cell Lung Cancer in a Korean Population

Recently, genetic variants in the WNT signaling pathway have been reported to affect the survival outcome of Caucasian patients with early stage non-small cell lung cancer (NSCLC). We therefore attempted to determine whether these same WNT signaling pathway gene variants had similar impacts on the survival outcome of NSCLC patients in a Korean population. A total of 761 patients with stages I–IIIA NSCLC were enrolled in this study. Eight variants of WNT pathway genes were genotyped and their association with overall survival and disease-free survival were analyzed. None of the eight variants were significantly associated with overall survival or disease-free survival. There were no differences in survival outcome after stratifying the subjects according to age, gender, smoking status, and histological type. These results suggest that genetic variants in the WNT signaling pathway may not affect the survival outcome of NSCLC in a Korean population.     

Survival,Classifications, and Desmosomal Plaque Genes in Non-Small Cell Lung Cancer

Novel biomarkers are required to improve prognostic predictions obtained with lung cancer staging systems. This study of 62 surgically-treated Non-Small Cell Lung Cancer (NSCLC) patients had two objectives: i) to compare the predictive value of T-stage classifications between the 6^th and 7^th editions of the Tumor, Node, and Metastasis staging system (TNM); and ii) to examine the association of Pkp1 and/or Krt15 gene expression with survival and outcomes. Multivariate and Kaplan-Meier survival analyses were performed, examining the relationship of survival with T-stage, recurrence, and TNM-stage (by each TNM edition) and with the single/combined expression of Pkp1 and/or Krt15 genes. Five-year survival rates only significantly differed as a function of T-stage in patients without recurrence when estimated using the 6^th edition of the TNM classification and only in patients in pathologic TNM-stage IA using the 7^th. Overall survival for patients with elevated expression of both genes was 13.5 months in those with adenocarcinoma and 34.6 months in those with squamous cell carcinoma. Overall survival was 30.4 months in patients with Pkp1 gene upregulation and 30.9 months in those with Krt15 gene upregulation. In conclusion, survival estimations as a function of T-staging differed between the 6^th and 7^th editions of TNM. Overall survival differed according to the expression of Pkp1 and/or Krt15 genes, although this relationship did not reach statistical significance.     

Changes in the Demographics and Prognoses of Patients with Resected Non-Small Cell Lung Cancer: A 20-Year Experience at a Single Institution in Korea

The demographics and prognosis of non-small cell lung cancer patients have changed during the last few decades. We conducted this study to assess the change in demographics and prognosis in resected non-small cell lung cancer patients during a 20-yr single-institution study in Korea. We retrospectively reviewed the medical records of 2,076 non-small cell lung cancer patients who underwent pulmonary resection between 1990 and 2009. Their clinical characteristics and survival were analyzed over a five-year period. With time, the proportions of female, adenocarcinoma, stage IA, and lobectomy patients increased, whereas the proportions of male, squamous cell carcinoma, stage IIIA, and pneumonectomy patients decreased. These demographic changes caused improved prognosis. The five-year survival rate of all patients was 53.9%. The five-year survival rate increased from 31.9% in 1990-1994, to 43.6% in 1995-1999, 51.3% in 2000-2004, and 69.7% in 2005-2009 (P < 0.001). In conclusion, among patients with resected non-small cell lung cancer, the proportions of female, adenocarcinoma, stage IA, and lobectomy patients have increased, and the five-year survival rate has gradually improved during the last 20 yr in Korea.     

Whole-Genome Analysis in Korean Patients with Autoimmune Myasthenia Gravis

Purpose

The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component. However, no common genetic variants have been unequivocally linked to autoimmune MG. We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samples from a Korean Multicenter MG Cohort.

Materials and Methods

To determine new genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an Axiom™ Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patients and 150 neurologically normal controls.

Results

In total, 641 SNPs from five case-control associations showed p-values of less than 10^-5. From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis.

Conclusion

The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG. Our findings also encourage further studies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG.     

Surveillance of Stool Samples for the Presence of Enterobacter sakazakii among Korean People

Purpose

Enterobacter sakazakii (E. sakazakii) infections are an important cause of life-threatening meningitis, septicemia, and necrotizing enterocolitis in infants. Dried infant formula milk is an important vehicle for E. sakazakii infection. E. sakazakii was isolated in Korea from dried infant formula milk. Although E. sakazakii infection of infants may occur in Korea, its prevalence has not yet been documented. Therefore, we determined the prevalence of E. sakazakii and documented symptoms.

Materials and Methods

Between March and October 2006, 1,146 stool samples were collected from patients at Uijeongbu St. Mary''s Hospital. Each fecal swab was dissolved in 10 mL of buffered peptone solution, and enriched culture was streaked onto Druggan-Forsythe-Iversen (DFI) agar. Presumptive E. sakazakii colonies that exhibited a blue-green color during culture on DFI medium were selected. The identity of colonies that developed yellow pigment during culture on TSA was determined using the Vitek system and PCR.

Results

We isolated 4 E. sakazakii strains whose 16S rRNA sequence alignments had a similarity of 99% with those of 3 E. sakazakii ATCC strains.

Conclusion

This is the first report on isolation of E. sakazakii from stool samples and to document the symptoms of Korean patients.     

Polymorphisms of Glutathione S-Transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi 1 (GSTP1) Genes and Epithelial Ovarian Cancer Risk

Background: Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development. Objectives: We tested in this study whether the GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms alter the risk of EOC. Materials and methods: Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ² or Fisher’s exact test. Results: The frequencies of GSTP1 Ile/Ile (57.6% versus 45.5%, P = 0.03), GSTM1 null plus GSTP1 Ile/Ile (43.5% versus 25.8%; P = 0.03) and GSTM1 null plus GSTT1 null plus GSTP1 Ile/Ile (30.3% versus 7.7%; P = 0.007) genotypes were higher in patients than in controls. Individuals with the respective genotypes had a 1.80 (95% CI: 1.06–3.06), 2.38 (95% CI: 1.08–5.24) and 11.28 (95%CI: 1.95–65.30)-fold increased risks of EOC than those with the remaining genotypes. Conclusions: Our data present preliminary evidence that GSTM1, GSTT1 and GSTP1 polymorphisms, particularly in combination, constitute important inherited EOC determinants in individuals from Southeastern Brazil.     

A Trp33Arg mutation at exon 1 of the MYH9 gene in a Korean patient with May-Hegglin anomaly

In this report, we describe a Korean patient with May-Hegglin anomaly from a mutation of the MYH9 gene. The proband was a 21-year-old man with thrombocytopenia. He did not have a bleeding tendency. His neutrophil count was normal at 7490/mm3; however, the neutrophils contained abnormal basophilic inclusions in their cytoplasm. The platelet count was decreased at 15,000/mm3 with giant platelets. Coagulation test results were not remarkable. Direct sequencing of MYH9 revealed that he was heterozygous for a mutation in exon 1, which was a 97T>A substitution mutation affecting codon 33, substituting tryptophan with arginine (Trp33Arg). Family study showed that both of his parents had normal phenotype and genotypes, indicating a de novo occurrence of the mutation in the proband.     

The HLA-DRB1 Polymorphism is Associated With Atopic Dermatitis, but not Egg Allergy in Korean Children

Purpose

We investigated whether particular HLA-DRB1 polymorphisms contribute to egg allergy development in Korean children with atopic dermatitis (AD).

Methods

HLA-DRB1 alleles were determined by PCR-sequence-specific oligonucleotide (SSO) and PCR-single-strand conformation polymorphism (SSCP) methods in 185 patients with AD and 109 normal control (NC) subjects. AD patients were divided into two groups: 1) AD with egg allergy, consisting of 96 patients with egg allergies as determined by egg-specific immunoglobulin E (IgE) reactivity; and 2) AD without egg allergy, consisting of 89 patients without egg allergies. HLA-DRB1 alleles were classified into functional groups (A, De, Dr, E, Q, R, a). HLA-DRB1 phenotype and functional group frequencies in the AD, AD with egg allergy, and AD without egg allergy groups were compared with those in the NC group.

Results

The frequency of DRB1^*08:02 was decreased in the AD with egg allergy group compared with the AD without egg allergy group (2.1% vs. 10.1%, P=0.021), and DRB1^*15:01 was increased in the AD with egg allergy group compared with the AD without egg allergy group (22.9% vs. 11.2%, P=0.036). However, significance was lost after Bonferroni correction. HLA-DRB1^*11:01 had a significantly higher frequency in AD patients compared with NCs (12.4% vs. 1.8%, corrected P=0.048) and was regarded as a susceptibility factor associated with AD. DRB1^*08:03 was decreased in AD patients compared with NCs (10.8% vs. 19.3%, P=0.043). HLA-DRB1 functional group ''a'', which includes DRB1^*15:01, seemed to be associated with the development of egg allergy in AD (P=0.033), but this result was not significant after Bonferroni correction.

Conclusions

HLA-DRB1 polymorphism is not associated with egg allergy, but HLA-DRB1^*11:01 is associated with AD in Korean children.     

Disseminated penicilliosis in a Korean human immunodeficiency virus infected patient from Laos

Penicillium marneffei may cause life-threatening systemic fungal infection in immune-compromised patients and it is endemic in Southeast Asia. A 39-yr-old HIV-infected male, living in Laos, presented with fever, cough, and facial vesiculopapular lesions, which had been apparent for two weeks. CT scans showed bilateral micronodules on both lungs; Pneumocystis jirovecii was identified by bronchoscopic biopsy. Despite trimethoprim-sulfamethoxazole and anti-tuberculosis medications, the lung lesions progressed and the facial lesions revealed central umbilications. Biopsy of the skin lesions confirmed disseminated penicilliosis, with the culture showing P. marneffei hyphae and spores. The P. marneffei was identified by rRNA PCR. A review of the bronchoscopic biopsy indicated penicilliosis. The patient completely recovered after being prescribed amphotericin-B and receiving antiretroviral therapy. This is the first case of penicilliosis in a Korean HIV-infected patient. It is necessary to consider P. marneffei when immunocompromised patients, with a history of visits to endemic areas, reveal respiratory disease.